Status:
COMPLETED
A Phase 1 Open Label Trial of Intravenous Administration of MVA-BN-Brachyury Vaccine in Patients With Advanced Cancer
Lead Sponsor:
Bavarian Nordic
Conditions:
Solid Metastatic Tumor
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
A Phase 1 open label trial of intravenous administration of MVA-BN-Brachyury vaccine in patients with advanced cancer. Patients with metastatic or unresectable locally advanced malignant solid tumors ...
Eligibility Criteria
Inclusion
- Men and women \> 18 years old.
- Patients must be able to understand and be willing to sign a written informed consent document.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
- Eligible patients must have one of the histologically confirmed cancers and treatment history as described:
- Chordoma
- Symptomatic, unresectable, locally recurrent, or metastatic tumors are acceptable for enrollment, given that this represents incurable disease.
- Only curative interventions are required as prior therapy (surgery or definitive radiation) as no known systemic therapies have proven benefit.
- Non-Small Cell Lung Cancer
- Metastatic or incurable locally advanced.
- Disease progression after indicated targeted therapy (EGFR-mut, ALK-fusion, BRAF-mut).
- Disease progression after one regimen of chemotherapy and anti-PD-1/L1 therapy either sequentially or concurrently.
- Small Cell Lung Cancer
- Metastatic disease.
- Disease progression after 1st line chemotherapy.
- Breast
- Metastatic disease considered to be incurable.
- Triple negative - disease progression after first line chemotherapy.
- ER+ disease - must have had disease progression through at least 2 lines of hormonal therapy and at least 1 chemotherapy regimen.
- Her2+ disease - must have had disease progression after at least 2 Her2-targeted therapy containing regimens.
- ER+ and Her2+ - must meet requirements of each tumor marker subtype (see above).
- Ovarian
- Metastatic disease.
- Disease progression after treatment with platinum-based chemotherapy.
- Prostate
- Metastatic Castration Resistant Prostate Cancer (mCRPC) AND
- Disease progression after at least one line of treatment of abiraterone or enzalutamide and docetaxel.
- Colorectal
- Metastatic disease.
- Must have received chemotherapy regimens containing 5-FU, oxaliplatin, irinotecan, and EGFR-targeted antibodies when indicated (absence of RAS mutation) with evidence of disease progression or AEs that preclude further treatment with standard therapies.
- Pancreatic
- Metastatic disease.
- Disease progression after or intolerance to standard chemotherapy regimens of known benefit (FOLFIRINOX or Gemcitabine and Abraxane).
- Hepatocellular
- Incurable disease: liver only or metastatic.
- Disease progression after at least one systemic therapy of known benefit (e.g. sorafenib).
- Bladder
- Metastatic disease.
- At least one line of chemotherapy and immune checkpoint inhibitors second line.
- Kidney
- Metastatic disease.
- After VEGF inhibitors, immune check-point inhibitors, m-TOR inhibitors.
- Patients must have measurable or evaluable disease. Measurable disease is defined by RECIST 1.1. In the case of evaluable disease, patients should have cancer-related symptoms to justify risk.
- Evaluable disease is defined as any of the following:
- Elevated serum tumor marker known to be related to the patient's tumor.
- Clear radiographic or physical exam evidence of tumor which does not meet RECIST 1.1 measurement requirements.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Patients must have normal organ and bone marrow function as defined below:
- Renal function:
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
- Female CrCl = \[(140 - age in years) x weight in kg x 0.85\] / \[72 x serum creatinine in mg/dL\]
- Male CrCl = \[(140 - age in years) x weight in kg x 1.00\] / \[72 x serum creatinine in mg/dL\]
- Liver function:
- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 x the ULN.
- Total bilirubin ≤ 1.5 x ULN (in subjects with Gilbert's syndrome a total bilirubin ≤ 3.0 x ULN), or \< 5 x ULN, if liver metastases are present.
- Hematological parameters (within one week of starting therapy):
- Hemoglobin \> 9 g/dL.
- Platelet count ≥ 100,000/µL.
- Absolute neutrophil count (ANC) ≥ 1/ µL.
- Troponin I within normal limits.
- Electrocardiogram (ECG) without clinically significant findings.
- Any prior chemotherapy, immunotherapy and/or radiation must be completed at least 4 weeks prior to the first planned dose of MVA-BN-Brachyury vaccine, with the following exceptions, assuming any toxicity related to these therapies is well controlled or resolved and the patient has been on that therapy for at least 8 weeks at the time of enrollment:
- Prostate cancer - patients must continue to receive Gonadotropin-Releasing-Hormone (GnRH) agonist or antagonist therapy (unless orchiectomy has been done). Patients on abiraterone or enzalutamide may continue those therapies.
- Breast cancer - patients may remain on hormonal therapy if indicated (Estrogen Receptor/Progesterone Receptor positive \[ER/PR+\]).
- A minimum of 6 weeks from any prior antibody therapies (such as ipilimumab or anti-Programmed Death 1/Programmed Death Ligand 1\[PD1/PD-L1\]) is required due to prolonged half-life.
- Patients must have recovered (grade 1 or baseline) from any clinically significant toxicity associated with prior therapy.
- Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 48 hours prior to administration of MVA-BN-Brachyury vaccine. Both men and women must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) through the trial treatment period and for at least three months after the last vaccination with MVA-BN-Brachyury vaccine.
Exclusion
- Receipt of an investigational agent within 28 days of the first planned dose of MVA-BN-Brachyury vaccine.
- Concurrent chemotherapy or radiotherapy or other immunotherapy not explicitly allowed by inclusion criteria for this trial.
- Known metastatic disease to the central nervous system, unless previously treated and well controlled for at least 3 months (clinically stable, no edema, no steroid treatment required).
- History of anaphylaxis or severe allergic reaction to any vaccine, aminoglycoside antibiotics or egg products.
- Active infection within 72 hours prior to vaccination.
- Administration of antibiotics within 7 days prior to initial vaccination.
- Subjects having known evidence of being immunocompromised as listed below:
- Human immunodeficiency virus (HIV) positivity, active chronic hepatitis infection, including B and C.
- Active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, and psoriasis not requiring systemic treatment are permitted.
- Immunosuppressive therapy for post-organ transplant.
- Chronic administration (defined as \> 5 consecutive days of \> 15 mg of prednisone (or equivalent) per day) of systemic corticosteroids within 14 days of the first planned dose of MVA-BN-Brachyury vaccine. Use of inhaled steroids, nasal sprays, eye drops, and topical creams is allowed. Steroids premedication for CT scans is allowed.
- Vaccinations or planned vaccinations with a live vaccine within 30 days prior to the trial vaccination or with an inactivated vaccine within 14 days prior to the trial vaccination.
- Patients with history of myocardial infarction, unstable angina pectoris, history of or existing CHF (NYHA Class II -IV), other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, poorly controlled hypertension and hemodynamic effective pericardial effusion.
- Known history of, or any evidence of active, non-infectious pneumonitis or primary pulmonary fibrosis.
- Psychiatric illness/social situations that, in the opinion of the Investigator, would limit compliance with trial requirements.
- Pregnant or breastfeeding women.
- Any other condition, which in the opinion of the Investigator, would indicate the subject is a poor candidate for treatment with MVA-BN-Brachyury vaccine or would interfere with the evaluation of the trial endpoints.
Key Trial Info
Start Date :
January 8 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 6 2021
Estimated Enrollment :
13 Patients enrolled
Trial Details
Trial ID
NCT04134312
Start Date
January 8 2020
End Date
April 6 2021
Last Update
July 14 2021
Active Locations (1)
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1
National Cancer Institute
Bethesda, Maryland, United States, 20892